In order to strengthen the structure and modify the function of a lipid bimolecular membrane such as a liposome, surface reformation (modification) is an important consideration. Known methods of introducing a functional compound like a protein to a lipid bimolecular membrane such as a liposome involve using a non-covalent bond or using a covalent bond. Considering the strength of the bond and the stability of the membrane, among other things, the covalent bond method is more useful.
Generally, the method of using a covalent bond involves combining the surface of a lipid bimolecular membrane with a chosen molecule for forming a covalent bond using a divalent crosslinking agent and practically, an amino group or an SH group on a protein, or a sugar chain is utilized as a functional group for the bonding.
More specifically, a method of using an SH group involves a method of bonding using a maleinimido group as a crosslinking agent via a Michael addition reaction for the maleinimido group (Biochimica et Biophysica Acta, 943, 53 (1988)), a method of bonding an antibody activated by N-succinimidyl-3-(2-pyridyldithio)propionyl phosphatidylethanolamine and N-succinimidyl-3-(2-pyridyldithio) propionate (Nature, 288, 602 (1980)), and a method of bonding using an .alpha.-haloketone group as the crosslinking agent via a nucleophilic displacement reaction for the group (European Patent 0,312,212). A method of utilizing sugar chains involves a method of incorporating a glycolipid into the membrane side of the lipid bimolecular membrane, cutting the glycolipid with periodic acid, and reacting the aldehyde formed with an amino group (Science, 210, 539 (1980)).
However, these methods all require a considerable number of steps and they can only be used for specific reactions.
It is also known to add a functional group to a lipid bimolecular membrane such as a liposome using a single-strand lipid membrane structural material which can be easily synthesized, as disclosed in JP-A-61-112021, JP-A-62-201864, JP-A-62-209092, and JP-A-1-27637 (the term "JP-A" as used herein means an "unexamined published Japanese patent application"). However, since a single-strand lipid membrane structural material is a reverse corn type molecule wherein the hydrophilic portion is more bulky than the hydrophobic portion, it has a disadvantage of being easily released from the membrane component in which case it would become a membrane poison.
Thus, there is great demand for a lipid membrane structural material that can be easily used to modify the surface of a lipid bimolecular membrane, has a variety of applications, and is safe for living organisms.